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Congenital disorder of glycosylation type Ia

Congenital disorder of glycosylation type Ia

Reviewed July 2010

What is congenital disorder of glycosylation type Ia?

Congenital disorder of glycosylation type Ia (CDG-Ia), also known as phosphomannomutase 2 deficiency, is an inherited condition that affects many parts of the body. The type and severity of problems associated with CDG-Ia vary widely among affected individuals, sometimes even among members of the same family.

Individuals with CDG-Ia typically develop signs and symptoms of the condition during infancy. Affected infants may have weak muscle tone (hypotonia), retracted (inverted) nipples, an abnormal distribution of fat, eyes that do not look in the same direction (strabismus), developmental delay, and a failure to gain weight and grow at the expected rate (failure to thrive). Infants with CDG-Ia also frequently have an underdeveloped cerebellum, which is the part of the brain that coordinates movement. Distinctive facial features are sometimes present in affected individuals, including a high forehead, a triangular face, large ears, and a thin upper lip. Children with CDG-Ia may also have elevated liver function tests, seizures, fluid around the heart (pericardial effusion), and blood clotting disorders. About 20 percent of affected infants do not survive the first year of life due to multiple organ failure.

The most severe cases of CDG-Ia are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Most babies with hydrops fetalis are stillborn or die soon after birth.

People with CDG-Ia who survive infancy may have moderate intellectual disability, and some are unable to walk independently. Affected individuals may also experience stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis. Recovery from these episodes usually occurs over a period of a few weeks to several months.

During adolescence or adulthood, individuals with CDG-Ia have reduced sensation and weakness in their arms and legs (peripheral neuropathy), an abnormal curvature of the spine (kyphoscoliosis), impaired muscle coordination (ataxia), and joint deformities (contractures). Some affected individuals have an eye disorder called retinitis pigmentosa that causes vision loss. Females with CDG-Ia have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, females with CDG-Ia do not go through puberty. Affected males experience normal puberty but often have small testes.

How common is congenital disorder of glycosylation type Ia?

More than 800 individuals with CDG-Ia have been identified worldwide.

What genes are related to congenital disorder of glycosylation type Ia?

Mutations in the PMM2 gene cause CDG-Ia. This gene provides instructions for making an enzyme called phosphomannomutase (PMM). The PMM enzyme is involved in a process called glycosylation, which attaches groups of sugar molecules (oligosaccharides) to proteins. Glycosylation modifies proteins so they can perform a wider variety of functions. Mutations in the PMM2 gene lead to the production of an abnormal PMM enzyme with reduced activity. Without a properly functioning PMM enzyme, glycosylation cannot proceed normally. As a result, incorrect oligosaccharides are produced and attached to proteins. The wide variety of signs and symptoms in CDG-Ia are likely due to the production of abnormally glycosylated proteins in many organs and tissues.

Read more about the PMM2 gene.

How do people inherit congenital disorder of glycosylation type Ia?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of congenital disorder of glycosylation type Ia?

These resources address the diagnosis or management of congenital disorder of glycosylation type Ia and may include treatment providers.

You might also find information on the diagnosis or management of congenital disorder of glycosylation type Ia in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about congenital disorder of glycosylation type Ia?

You may find the following resources about congenital disorder of glycosylation type Ia helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for congenital disorder of glycosylation type Ia?

  • carbohydrate-deficient glycoprotein syndrome type Ia
  • CDG1a
  • CDG Ia
  • CDGS1a
  • Jaeken syndrome
  • phosphomannomutase 2 deficiency
  • PMM2-CDG
  • PMM deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about congenital disorder of glycosylation type Ia?

Where can I find general information about genetic conditions?

What glossary definitions help with understanding congenital disorder of glycosylation type Ia?

References (6 links)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

 
Reviewed: July 2010
Published: December 16, 2014